Intestinal inflammation and its complications have a profound health and economic impact on industrialized nations, developing countries and the agriculture industry. In the United States alone, direct costs for inflammatory bowel disease were as much as $2.6 billion in 1990. The purpose of the Center for Gastrointestinal Biology and Disease is to promote multidisciplinary research on mechanisms of inflammation and fibrosis in the liver and intestine as they relate to inflammatory bowel disease. In order to achieve this purpose the center brings together 26 clinical and basic science investigators from diverse disciplines and two universities to extend the effectiveness of research related to center themes. During the previous five years center-based research was enhanced by the existence of 4 scientific core laboratories that provided technical support, laboratory animals, or assays - Immunoassay, Molecular Biology, Biostatistics, Gnotobiotic Animal and Piglet. Broad use of these cores significantly improved the productivity and efficiency of center members. In the current application we propose a new Cell Culture Core to further extend our capabilities. An ambitious Pilot/Feasibility Program has provided startup funds to junior investigators and to established investigators wishing to pursue new directions in research. A Scientific Enrichment Program, consisting of seminars, symposia and workshops, has improved the intellectual climate for gastrointestinal biological research and has promoted collaboration and communication among involved personnel. Signs of success of this research center over the past eight years include: (l) the contributions of research conducted by center scientists on mechanisms of intestinal and hepatic inflammation and fibrosis; (2) the eight junior investigators who have received career development grants as a result of the center; and (3) the successful conversion of center pilot/feasibility studies into funded grants. Center members have been at the forefront in developing new animal models of granulomatous enterocolitis, sclerosing cholangitis and pouchitis; cloning and characterizing novel immunosuppressive molecules; exploring the ability of normal intestinal bacteria and bacterial products to induce and perpetuate intestinal and systemic inflammation; determining the molecular basis of fibrosis; developing primary enterocyte cell lines; understanding regulation of epithelial adaptation and repair; and conducting studies of the epidemiology, quality of life, and health care utilization of patients with inflammatory bowel disease. Two long term goals are to determine mechanisms of enhanced host susceptibility to chronic, relapsing enterocolitis and its fibrotic complications and to identify environmental factors which initiate and perpetuate intestinal and hepatic inflammation in the genetically susceptible host. The Center for Gastrointestinal Biology and Disease now seeks five additional years of support to continue to conduct the exciting research agenda that we have developed.